Irinotecan Plus Gemcitabine In Treating Patients With Unresectable Or Metastatic Solid Tumors

Study Overview

Irinotecan Plus Gemcitabine in Treating Patients With Unresectable or Metastatic Solid Tumors

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining irinotecan and gemcitabine in treating patients who have unresectable or metastatic solid tumors.

OBJECTIVES: * Determine the maximum tolerated dose (MTD) and the principal toxicities of irinotecan and gemcitabine in patients with surgically unresectable or metastatic solid tumors. * Determine if the principal toxicities and MTD of this combination regimen are affected by drug sequencing in this patient population. * Determine the potential for gemcitabine to alter the pharmacokinetic characteristics when administered with irinotecan in these patients. * Describe the influence effected by varying the administration sequence of this combination regimen in this patient population. * Obtain preliminary data regarding efficacy of this combination regimen in these patients. OUTLINE: This is a dose-escalation study. Patients receive irinotecan IV over 90 minutes followed by gemcitabine IV over 30 minutes on days 1 and 15. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Once the maximum tolerated dose (MTD) is reached, patients receive subsequent doses of the inverse sequence of the combination drugs until a new MTD is determined. Cohorts of 3-6 patients receive escalating doses of irinotecan and gemcitabine until the MTD is reached. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicities. Patients are followed every 3 months until death. PROJECTED ACCRUAL: At least 12 patients will be accrued for this study.

Bladder Cancer
Breast Cancer
Colorectal Cancer
Kidney Cancer
Lung Cancer
Pancreatic Cancer

DRUG: gemcitabine hydrochloride
DRUG: irinotecan hydrochloride

NU 98X3
NU-98X3
P-UPJOHN-976475157
NCI-G99-1588

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 1999-12-10	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2017-04-14
First Submitted that Met QC Criteria 2003-05-06	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2017-04-18
First Posted (ACTUAL) 2003-05-07	Results First Posted N/A	Last Verified 2017-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Irinotecan Plus Gemcitabine	DRUG: gemcitabine hydrochloride DRUG: irinotecan hydrochloride

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Irinotecan Plus Gemcitabine

DRUG: gemcitabine hydrochloride

DRUG: irinotecan hydrochloride

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologically confirmed metastatic or surgically unresectable solid tumor, having received the following maximum number of prior therapies for advanced disease:

Bladder cancer - no more than 1 prior therapy
Breast cancer - no more than 2 prior therapies
Colorectal cancer - no more than 1 prior therapy
Kidney cancer - no prior therapy
Lung cancer - no more than 1 prior therapy
Pancreatic cancer - no prior therapy
Bidimensionally measurable disease outside a previously irradiated field

At least 2 cm x 2 cm
No known bone metastases
CNS involvement allowed if successfully controlled by surgery or radiotherapy and not requiring corticosteroids
Hormone receptor status:

Not specified

18 and over

Not specified

ECOG 0-2

At least 3 months

Granulocyte count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

Bilirubin no greater than 1.5 mg/dL regardless of liver involvement secondary to tumor
SGOT no greater than 3 times upper limit of normal (ULN) (no greater than 5 times ULN if liver metastases present)
No known Gilbert's disease

Creatinine no greater than 1.8 mg/dL
Calcium less than 12.0 mg/dL

No myocardial infarction within the past 6 months
No congestive heart failure requiring therapy

No active uncontrolled bacterial, viral (including HIV), or invasive fungal infection
No psychiatric disorders that would prevent compliance
No other malignancy within the past 5 years except adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix
No history of seizures
Not pregnant or nursing
Fertile patients must use effective contraception

No concurrent sargramostim (GM-CSF)
No concurrent immunotherapy

No prior irinotecan, topotecan, or gemcitabine
Prior adjuvant chemotherapy allowed, if at least 1 year between last dose of adjuvant chemotherapy and recurrence of cancer
No other concurrent chemotherapy

Not specified

See Disease Characteristics
At least 4 weeks since prior radiotherapy to less than 30% of bone marrow
No prior whole pelvic radiotherapy
No concurrent radiotherapy

See Disease Characteristics

No concurrent phenytoin, phenobarbital, or other antiepileptic prophylaxis

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

STUDY_CHAIR: Al B. Benson, MD, FACP, Robert H. Lurie Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Wisinski KB, Mulcahy MF, Newman S, et al.: A phase I study of irinotecan and gemcitabine in solid tumors. [Abstract] American Society of Clinical Oncology 2007 Gastrointestinal Cancers Symposium, 19 -21 January 2007, Orlando, Florida A-140, 2007.

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Resources

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Caregivers

Clinical Trial Record